MARVEL on RT mutations at position 221

H221Y is a nonpolymorphic accessory NNRTI-selected mutation that frequently occurs in combination with Y181C. Alone it has minimal detectable effects on NNRTI susceptibility. It is frequently selected in patients receiving RPV (Rimsky 2012, Tibotec 2012).

Mutation

EFV

NVP

ETR

RPV

H221Y

10

10

10

10

Footnote:Mutation scores on the left are derived from published literature linking mutations and ARVs (the complete details can be found in the HIVdb Release Notes).

Genotype-treatment correlation

Mutation frequency according to subtype and drug-class experience.

The frequency of each mutation at position 221 according to subtype and drug-class experience. Data are shown for the 8 most common subtypes. The number of persons in each subtype/treatment category is shown beneath the subtype. Mutations occurring at a frequency >0.5% are shown. Each mutation is also a hyper-link to a separate web page with information on each isolate, including literature references with PubMed abstracts, the GenBank accession number, and complete sequence and treatment records.

The first row shows the frequency of the mutation in persons who are RTI-naive (indicated in green). The second row shows the frequency of the mutation in persons who have received one or more NRTIs (No NNRTIs). The third row shows the frequency of the mutation in persons who have received one or more NNRTIs (+/- NRTIs). The following rows show the frequency of the mutation in persons who have received only a single NNRTI. Mutation rates that differ significantly between treated and untreated isolates are indicated in yellow.

Mutation

NRTI

NNRTI

NumSeq

NumMut

% Mutant

p

H221C

0

0

59910

0

H221C

>=1

>=0

26648

20

0.00

0.000

H221C

AZT

>=0

417

0

H221C

DDI

>=0

52

0

H221C

D4T

>=0

53

0

H221C

ABC

>=0

5

0

H221C

D4T+3TC

>=0

3683

1

0.00

0.058

H221C

AZT+3TC

>=0

2733

5

0.10

0.000

H221C

D4T+DDI

>=0

456

1

0.20

0.000

H221C

AZT+DDI

>=0

557

0

H221C

ABC+3TC

>=0

333

0

H221C

TDF+3TC

>=0

589

0

H221C

TDF+FTC

>=0

395

0

Mutation

NRTI

NNRTI

NumSeq

NumMut

% Mutant

p

H221L

0

0

59910

9

0.00

H221L

>=1

>=0

26648

24

0.00

0.000

H221L

AZT

>=0

417

0

H221L

DDI

>=0

52

0

H221L

D4T

>=0

53

0

H221L

ABC

>=0

5

0

H221L

D4T+3TC

>=0

3683

8

0.20

0.000

H221L

AZT+3TC

>=0

2733

2

0.00

0.132

H221L

D4T+DDI

>=0

456

2

0.40

0.000

H221L

AZT+DDI

>=0

557

0

H221L

ABC+3TC

>=0

333

0

H221L

TDF+3TC

>=0

589

0

H221L

TDF+FTC

>=0

395

0

Mutation

NRTI

NNRTI

NumSeq

NumMut

% Mutant

p

H221P

0

0

59910

11

0.00

H221P

>=1

>=0

26648

6

0.00

0.888

H221P

AZT

>=0

417

0

H221P

DDI

>=0

52

0

H221P

D4T

>=0

53

0

H221P

ABC

>=0

5

0

H221P

D4T+3TC

>=0

3683

1

0.00

0.810

H221P

AZT+3TC

>=0

2733

2

0.00

0.205

H221P

D4T+DDI

>=0

456

2

0.40

0.000

H221P

AZT+DDI

>=0

557

1

0.10

0.239

H221P

ABC+3TC

>=0

333

0

H221P

TDF+3TC

>=0

589

0

H221P

TDF+FTC

>=0

395

0

Mutation

NRTI

NNRTI

NumSeq

NumMut

% Mutant

p

H221Q

0

0

59910

10

0.00

H221Q

>=1

>=0

26648

4

0.00

0.913

H221Q

AZT

>=0

417

0

H221Q

DDI

>=0

52

0

H221Q

D4T

>=0

53

0

H221Q

ABC

>=0

5

0

H221Q

D4T+3TC

>=0

3683

0

H221Q

AZT+3TC

>=0

2733

0

H221Q

D4T+DDI

>=0

456

0

H221Q

AZT+DDI

>=0

557

0

H221Q

ABC+3TC

>=0

333

0

H221Q

TDF+3TC

>=0

589

0

H221Q

TDF+FTC

>=0

395

1

0.20

0.110

Mutation

NRTI

NNRTI

NumSeq

NumMut

% Mutant

p

H221R

0

0

59910

11

0.00

H221R

>=1

>=0

26648

1

0.00

0.170

H221R

AZT

>=0

417

0

H221R

DDI

>=0

52

0

H221R

D4T

>=0

53

0

H221R

ABC

>=0

5

0

H221R

D4T+3TC

>=0

3683

0

H221R

AZT+3TC

>=0

2733

2

0.00

0.205

H221R

D4T+DDI

>=0

456

0

H221R

AZT+DDI

>=0

557

0

H221R

ABC+3TC

>=0

333

0

H221R

TDF+3TC

>=0

589

0

H221R

TDF+FTC

>=0

395

0

Mutation

NRTI

NNRTI

NumSeq

NumMut

% Mutant

p

H221Y

0

0

59910

42

0.00

H221Y

>=1

>=0

26648

1595

5.90

0.000

H221Y

AZT

>=0

417

0

H221Y

DDI

>=0

52

1

1.90

0.016

H221Y

D4T

>=0

53

1

1.80

0.018

H221Y

ABC

>=0

5

3

60.00

0.000

H221Y

D4T+3TC

>=0

3683

346

9.30

0.000

H221Y

AZT+3TC

>=0

2733

102

3.70

0.000

H221Y

D4T+DDI

>=0

456

24

5.20

0.000

H221Y

AZT+DDI

>=0

557

9

1.60

0.000

H221Y

ABC+3TC

>=0

333

21

6.30

0.000

H221Y

TDF+3TC

>=0

589

40

6.70

0.000

H221Y

TDF+FTC

>=0

395

14

3.50

0.000

Footnote: About one-half of the untreated isolates belong to non-subtype B isolates; About 20% of the treated isolates belong to non-subtype B isolates; A page containing summaries for all of the mutations at this position can be found here.

Genotype-phenotype correlation

Phenotypes of top 10 common patterns of drug resistance mutations with mutations at position 221.

Mutation pattern data is not available for H221.

A complete summary of additional in vitro susceptibility data for viruses with H221 obtained using other assays including the Antivirogram can be found here.

Phenotypic coefficients using machine learning

Least Square Regression (LSR) was used to learn the relative contribution of each mutation to the fold decrease in susceptibility for an ARV. The figure on the left (click to enlarge the figure) shows the regression coefficients (which correlate with the contribution to resistance) for the 24 nonpolymorphic NNRTI-resistance mutations shown to contribute decreased susceptibility to at least one NNRTI. A complete description of the method that generates this figure can be found at Rhee et al PNAS 2006.